Frontiers and hotspots in hand, foot, and mouth disease research during 2006 to 2023: A bibliometric and visual analysis.

BACKGROUND: Enteroviruses-infected hand, foot, and mouth disease (HFMD) seriously threatens human health. This study aimed to analyze the research status, hotspots, and frontiers of HFMD. METHODS: Publications on HFMD between January 1, 2006, and January 31, 2023, were retrieved from the Web of Science Core database. Bibliometric tools, including CiteSpace, VOSviewer, R package "Bibiometrix," SCImago Graphica, and Charticulator, were utilized to analyze and visualize the data. RESULTS: A total of 1860 articles from 424 journals, involving 8815 authors from 64 countries and 1797 institutions were analyzed. The number of studies on HFMD has shown an increasing trend over the past 18 years, with an annual increase observed since 2006, which is particularly prominent after 2010. Research in this field has centered on the Asian region. Notably, the research hotspots were mainly focused on vaccines, epidemiology, and pathogenesis of HFMD. Among the researchers in this field, Zhang Yong emerged as the most prolific author, while Xu Wenbo had the most significant influence. The Chinese Academy of Sciences was the most productive institution, and China was the most productive country for HFMD research. CONCLUSION: By bibliometric analysis, researchers in the HMFD field can efficiently identify and visually represent their research focus and limitations. In the future, it is crucial to maintain ongoing surveillance of HFMD outbreaks and their pathogenic changes. Additionally, future research should extensively explore the molecular mechanisms underlying Enteroviruses-induced HFMD with a focus on developing vaccines and therapies.

Multi-grained visual pivot-guided multi-modal neural machine translation with text-aware cross-modal contrastive disentangling.

The goal of multi-modal neural machine translation (MNMT) is to incorporate language-agnostic visual information into text to enhance the performance of machine translation. However, due to the inherent differences between image and text, these two modalities inevitably suffer from semantic mismatch problems. To tackle this issue, this paper adopts a multi-grained visual pivot-guided multi-modal fusion strategy with cross-modal contrastive disentangling to eliminate the linguistic gaps between different languages. By using the disentangled multi-grained visual information as a cross-lingual pivot, we can enhance the alignment between different languages and improve the performance of MNMT. We first introduce text-guided stacked cross-modal disentangling modules to progressively disentangle image into two types of visual information: MT-related visual and background information. Then we effectively integrate these two kinds of multi-grained visual elements to assist target sentence generation. Extensive experiments on four benchmark MNMT datasets are conducted, and the results demonstrate that our proposed approach achieves significant improvement over the other state-of-the-art (SOTA) approaches on all test sets. The in-depth analysis highlights the benefits of text-guided cross-modal disentangling and visual pivot-based multi-modal fusion strategies in MNMT. We release the code at https://github.com/nlp-mnmt/ConVisPiv-MNMT.

The long-term spatio-temporal trends in burden and attributable risk factors of major depressive disorder at global, regional and national levels during 1990-2019: a systematic analysis for GBD 2019.

AIMS: Caused by multiple risk factors, heavy burden of major depressive disorder (MDD) poses serious challenges to public health worldwide over the past 30 years. Yet the burden and attributable risk factors of MDD were not systematically known. We aimed to reveal the long-term spatio-temporal trends in the burden and attributable risk factors of MDD at global, regional and national levels during 1990-2019. METHODS: We obtained MDD and attributable risk factors data from Global Burden of Disease Study 2019. We used joinpoint regression model to assess the temporal trend in MDD burden, and age-period-cohort model to measure the effects of age, period and birth cohort on MDD incidence rate. We utilized population attributable fractions (PAFs) to estimate the specific proportions of MDD burden attributed to given risk factors. RESULTS: During 1990-2019, the global number of MDD incident cases, prevalent cases and disability-adjusted life years (DALYs) increased by 59.10%, 59.57% and 58.57%, respectively. Whereas the global age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR) and age-standardized DALYs rate (ASDR) of MDD decreased during 1990-2019. The ASIR, ASPR and ASDR in women were 1.62, 1.62 and 1.60 times as that in men in 2019, respectively. The highest age-specific incidence, prevalence and DALYs rate occurred at the age of 60-64 in women, and at the age of 75-84 in men, but the maximum increasing trends in these age-specific rates occurred at the age of 5-9. Population living during 2000-2004 had higher risk of MDD. MDD burden varied by socio-demographic index (SDI), regions and nations. In 2019, low-SDI region, Central sub-Saharan Africa and Uganda had the highest ASIR, ASPR and ASDR. The global PAFs of intimate partner violence (IPV), childhood sexual abuse (CSA) and bullying victimization (BV) were 8.43%, 5.46% and 4.86% in 2019, respectively. CONCLUSIONS: Over the past 30 years, the global ASIR, ASPR and ASDR of MDD had decreased trends, while the burden of MDD was still serious, and multiple disparities in MDD burden remarkably existed. Women, elderly and populations living during 2000-2004 and in low-SDI regions, had more severe burden of MDD. Children were more susceptible to MDD. Up to 18.75% of global MDD burden would be eliminated through early preventing against IPV, CSA and BV. Tailored strategies-and-measures in different regions and demographic groups based on findings in this studywould be urgently needed to eliminate the impacts of modifiable risk factors on MDD, and then mitigate the burden of MDD.

Porphyromonas gingivalis OMVs promoting endothelial dysfunction via the STING pathway in periodontitis.

OBJECTIVE: This study aimed to assess the effects of Porphyromonas gingivalis outer membrane vesicles (Pg-OMVs) in chronic periodontitis and explore the underlying mechanism involved. METHODS: In vitro, Pg-OMVs were incubated with Ea.hy926 (vessel endothelial cells, ECs) to evaluate their effects on endothelial functions and to investigate the underlying mechanism. The effects of endothelial dysfunction on MG63 osteoblast-like cells were verified using an indirect co-culture method. For in vivo studies, micro-CT was conducted to identify alveolar bone mass. Immunofluorescence staining was conducted to confirm the levels of stimulator of interferon genes (STING) in the blood vessel and the number of Runx2+ cells around the alveolar bone. RESULTS: Pg-OMVs were endocytosed by ECs, leading to endothelial dysfunction. The cGAS-STING-TBK1 pathway was activated in ECs, which subsequently inhibited MG63 migration and early osteogenesis differentiation. In vivo, Pg-OMVs promoted alveolar bone resorption, increased STING levels in the blood vessel, and decreased Runx2+ cells around the alveolar bone. CONCLUSIONS: Pg-OMVs caused endothelial dysfunction and activated the cGAS-STING-TBK1 signal cascade in ECs, thereby impairing ECs-mediated osteogenesis. Furthermore, Pg-OMVs aggregated alveolar bone loss and altered the blood vessel-mediated osteogenesis with elevated STING.

Au/Doc/Quer@PDA/A10-3.2 Nanoparticles for targeted treatment of docetaxel-resistant prostate cancer.

Docetaxel (Doc), as a first-line chemotherapy drug for prostate cancer (PC), often loses its therapeutic efficacy due to acquired resistance and lack of targeting specificity. Therefore, there is a need to develop a novel drug that can overcome Doc resistance and enhance its targeting ability to inhibit PC progression. In this study, we prepared Au/Doc/Quer@PDA/A10-3.2 nanoparticles (NPs) composite drug by encapsulating Doc and quercetin (Quer) within polydopamine (PDA)-coated Au NPs and further modifying them with RNA oligonucleotide aptamer A10-3.2. A10-3.2 was used for specific targeting of prostate-specific membrane antigen (PSMA)-positive PC cells (LNCaP). Quer was employed to reverse the resistance of Doc-resistant cell line (LNCaP/R) to Doc. Physical characterization using ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR) confirmed the successful preparation of Au/Doc/Quer@PDA/A10-3.2 NPs. Fluorescence imaging and flow cytometry experiments demonstrated the targeting ability of Au/Doc/Quer@PDA/A10-3.2 NPs towards PSMA-positive LNCaP/R cells. Cell proliferation, apoptosis, invasion, and migration experiments revealed that Quer reversed the resistance of LNCaP/R cells to Doc. Immunoblotting experiments further confirmed the mechanism behind sensitization of chemotherapy by Quer. Finally, we evaluated the therapeutic efficacy of Au/Doc/Quer@PDA/A10-3.2 NPs in a mouse model of PC. In conclusion, this study synthesized and validated a novel nano-composite drug (Au/Doc/Quer@PDA/A10-3.2 NPs) for combating Doc-resistant PC, which could potentially be applied in clinical treatment of PC.

Resveratrol Inhibits VDAC1-Mediated Mitochondrial Dysfunction to Mitigate Pathological Progression in Parkinson's Disease Model.

An increase in α-synuclein (α-syn) levels and mutations in proteins associated with mitochondria contribute to the development of familial Parkinson's disease (PD); however, the involvement of α-syn and mitochondria in idiopathic PD remains incompletely understood. The voltage-dependent anion channel I (VDAC1) protein, which serves as a crucial regulator of mitochondrial function and a gatekeeper, plays a pivotal role in governing cellular destiny through the control of ion and respiratory metabolite flux. The ability of resveratrol (RES), which is a potent phytoalexin with antioxidant and anti-inflammatory properties, to regulate VDAC1 in PD is unknown. The objective of this study was to evaluate the role of VDAC1 in the pathological process of PD and to explore the mechanism by which resveratrol protects dopaminergic neurons by regulating VDAC1 to maintain the mitochondrial permeability transition pore (mPTP) and calcium ion balance. The effects of RES on the motor and cognitive abilities of A53T mice were evaluated by using small animal behavioral tests. Various techniques, including immunofluorescence staining, transmission electron microscopy, enzyme-linked immunoadsorption, quantitative polymerase chain reaction (PCR), and Western blotting, among others, were employed to assess the therapeutic impact of RES on neuropathy associated with PD and its potential in regulating mitochondrial VDAC1. The findings showed that RES significantly improved motor and cognitive dysfunction and restored mitochondrial function, thus reducing oxidative stress levels in A53T mice. A significant positive correlation was observed between the protein expression level of VDAC1 and mitochondrial α-syn expression, as well as disease progression, whereas no such correlation was found in VDAC2 and VDAC3. Administration of RES resulted in a significant decrease in the protein expression of VDAC1 and in the protein expression of α-syn both in vivo and in vitro. In addition, we found that RES prevents excessive opening of the mPTP in dopaminergic neurons. This may prevent the abnormal aggregation of α-syn in mitochondria and the release of mitochondrial apoptosis signals. Furthermore, the activation of VDAC1 reversed the resveratrol-induced decrease in the accumulation of α-syn in the mitochondria. These findings highlight the potential of VDAC1 as a therapeutic target for PD and identify the mechanism by which resveratrol alleviates PD-related pathology by modulating mitochondrial VDAC1.

Rhizobial-induced phosphatase GmPP2C61A positively regulates soybean nodulation.

Symbiotic nitrogen fixation (SNF) is crucial for legumes, providing them with the nitrogen necessary for plant growth and development. Nodulation is the first step in the establishment of SNF. However, the determinant genes in soybean nodulation and the understanding of the underlying molecular mechanisms governing nodulation are still limited. Herein, we identified a phosphatase, GmPP2C61A, which was specifically induced by rhizobia inoculation. Using transgenic hairy roots harboring GmPP2C61A::GUS, we showed that GmPP2C61A was mainly induced in epidermal cells following rhizobia inoculation. Functional analysis revealed that knockdown or knock-out of GmPP2C61A significantly reduced the number of nodules, while overexpression of GmPP2C61A promoted nodule formation. Additionally, GmPP2C61A protein was mainly localized in the cytoplasm and exhibited conserved phosphatase activity in vitro. Our findings suggest that phosphatase GmPP2C61A serves as a critical regulator in soybean nodulation, highlighting its potential significance in enhancing symbiotic nitrogen fixation.

CRYL1 is a Potential Prognostic Biomarker of Clear Cell Renal Cell Carcinoma Correlated with Immune Infiltration and Cuproptosis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a widespread urogenital neoplasm. However, the therapeutic efficacy of these methods is unsatisfactory. In-depth screening of biomarkers could aid early diagnosis and therapy and predict patient prognosis. METHODS: The GEO datasets were selected with specific criteria. Differentially expressed gene (DEG), weighted gene coexpression network analysis (WGCNA), protein-protein interaction, LASSO, random forest, and Cox regression analyses were applied to identify the independent prognostic biomarkers. Survival analysis, correlation with clinical features, gene set enrichment analysis (GSEA), GO enrichment, immune infiltration analysis, and correlation with cuproptosis-related genes were carried out to determine the prognostic value and possible molecular mechanisms of the TSVR. Wound healing assays, transwell assays, cell colony formation experiments, flow cytometry, and immunohistochemistry (IHC) analysis were used to validate the functional attributes of CRYL1. RESULTS: Four GEO datasets were included to screen for hub genes. DEG combined with WGCNA showed a key module with 300 genes having the strongest correlation with "survival state" (R2 = -0.24 and P = 7e-8); six genes were identified by LASSO, random forest, and Cytoscape. Finally, CRYL1 (hazard ratio (HR) = 2.01, P < 0.001) was selected as an independent prognostic biomarker. The higher CRYL1 expression group had better DFS and overall survival (OS). GSEA demonstrated that the CRYL1-related DEGs were enriched mainly in the metabolism of sugar, fat, and amino acids. CRYL1 is positively correlated with FDX1 and the LIAS pathway, which are important molecule involved in cuproptosis. CRYL1 affects the infiltration abundance of four immune cells and can predict a positive OS. Wound healing, transwell, cell colony formation, and flow cytometry assays demonstrated that CRYL1 silencing enhances migration and proliferation and leads to a decreased apoptotic ratio. IHC analysis suggested that CRYL1 was highly expressed in adjacent tissues. CONCLUSIONS: CRYL1 is a robust predictive marker for clinicopathological characteristics and survival status in ccRCC patients.

Intratumoral Delivery of Interleukin 9 via Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in Tumor Models.

The success of cancer immunotherapy is largely associated with immunologically hot tumors. Approaches that promote the infiltration of immune cells into tumor beds are urgently needed to transform cold tumors into hot tumors. Oncolytic viruses can transform the tumor microenvironment (TME), resulting in immunologically hot tumors. Cytokines are good candidates for arming oncolytic viruses to enhance their function in this transformation. Here, we used the oncolytic vaccinia virus (oVV) to deliver interleukin-9 (IL-9) into the tumor bed and explored its antitumor effects in colon and lung tumor models. Our data show that IL-9 prolongs viral persistence, which is probably mediated by the up-regulation of IL-10. The vvDD-IL-9 treatment elevated the expression of Th1 chemokines and antitumor factors such as IFN-γ, granzyme B, and perforin. IL-9 expression increased the percentages of CD4+ and CD8+ T cells in the TME and decreased the percentage of oVV-induced immune suppressive myeloid-derived suppressor cells (MDSC), leading to potent antitumor effects compared with parental virus treatment. The vvDD-IL-9 treatment also increased the percentage of regulatory T cells (Tregs) in the TME and elevated the expression of immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4, but not GITR. The combination therapy of vvDD-IL-9 and the anti-CTLA-4 antibody, but not the anti-GITR antibody, induced systemic tumor-specific antitumor immunity and significantly extended the overall survival of mice, indicating a potential translation of the IL-9-expressing oncolytic virus into a clinical trial to enhance the antitumor effects elicited by an immune checkpoint blockade for cancer immunotherapy.

Treg-Related Genes Representing a Potential Shared Biological Mechanism Between Clear Cell Renal Carcinoma and Obesity.

OBJECTIVE: To determine the potential shared biological mechanism between obesity and clear cell renal carcinoma (ccRCC). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Urology, Lishui People's Hospital, Lishui City, China, from December 2022 to March 2023. METHODOLOGY: The test and validation cohorts were selected from the GEO database. WGCNA and PPI networks were applied to identify shared hub genes. GO/KEGG, GSEA, and ROC curve analyses were applied to explore the potential underlying mechanisms and diagnostic power. Logistic regression was used to select genes to construct the signature. The risk score and various immune-related analyses were performed to assess the clinical and immune performance of the signature. The CellMiner platform was used to screen potential FDA-approved drugs. RESULTS: PTPRC, TYROBP, ITGB2, CD86, and ITGAM were defined as shared hub genes with good diagnostic power for obesity and ccRCC. Eight immune cells exhibited a positive correlation with the hub genes, while two immune cells showed negative associations. MDSCs and Tregs had the strongest positive associations with the hub genes. The Treg-related pathway exhibited predominant enrichment. The TYROBP, ITGB2, and CD86 genes were selected to construct an immune signature that has good clinical and immune performance. Six FDA-approved drugs were screened. CONCLUSION: Five Treg-related genes were identified as shared hub genes in obese patients and ccRCC patients. A signature was constructed to describe the immune features of ccRCC. KEY WORDS: Treg-related genes, Shared biological mechanism, Immune signature, Obesity, Clear cell renal carcinoma (ccRCC).

The augmentation of cytotoxic immune cell functionality through physical exertion bolsters the potency of chemotherapy in models of mammary carcinoma.

BACKGROUND: Mammary carcinoma, a pervasive and potentially lethal affliction, is conjectured to be profoundly influenced by physical exercise, both in prophylaxis and therapeutic contexts. This study endeavors to explore the repercussions of exercise training on the progression of mammary carcinoma, particularly the mechanisms by which the amalgamation of an exercise regimen and doxorubicin induces tumor cell apoptosis. METHODS: Female BALB/c mice were categorized into four distinct groups: A sedentary group (SED), an exercise group (Ex), a doxorubicin group (Dox, 5 mg/kg), and a combined treatment group (Dox + Ex). The exercise training lasted for 21 days and included aerobic rotarod exercise and resistance training. The impact of exercise training on tumor growth, immune cell proportions, inflammatory factor levels, and cell apoptosis pathway was assessed. RESULTS: Exercise training significantly curtailed tumor growth in a mouse model of breast cancer. Both the Ex and Dox groups exhibited significant reductions in tumor volume and weight (p < 0.01) in comparison to the SED group, while the Dox + Ex group had a significantly lower tumor volume and weight than the Dox group (p < 0.01). Exercise training also significantly increased the proportion of NK and T cells in various parts of the body and tumor tissue, while decreasing tumor blood vessels density. Exercise training also increased IL-6 and IL-15 levels in the blood and altered the expression of apoptosis-related proteins in tumor tissue, with the combined treatment group showing even more significant changes. CONCLUSIONS: Physical training improves the effectiveness of doxorubicin in treating breast cancer by activating cytotoxic immune cells, releasing tumor suppressor factors, and initiating mt-apoptosis, all while mitigating the adverse effects of chemotherapy.

Integrated multi-omics profiling highlights the benefits of resveratrol hydroxypropyl-ß-cyclodextrin inclusion complex for A53T transgenic mice through the microbiota-gut-brain axis.

Parkinson's disease (PD) is a neurological disorder characterized by motor and gastrointestinal dysfunctions. Resveratrol is a potent antioxidant and anti-inflammatory phytoalexin known for its health-promoting benefits. However, little is known about its potential in treating PD by modulating the microbial gut-brain axis, and its clinical application has been limited due to poor water solubility, rapid metabolism, and limited systemic bioavailability. Our study aimed to evaluate the therapeutic potential of RHSD, a resveratrol-cyclodextrin inclusion complex, in treating PD through the gut-brain axis in human SNCA-transgenic (A53T) mice PD models. Building on our previous study, we prepared RHSD and compared its efficacy with uncoated resveratrol for PD treatment. The study results demonstrated that RHSD exhibited several advantages in improving motor function, alleviating cognitive impairment, restoring intestinal barrier function, and inhibiting neuropathy. Subsequently, a series of analyses, including fecal microbiota metagenomic sequencing, non-target metabolic assays, host transcriptome sequencing, and integrative analysis were performed to reveal the potential therapeutic pathways of RHSD in A53T mice. The metagenomic sequencing results indicated a significant increase in the levels of Lactobacillus murinus, Lactobacillus reuteri, Enterorhabduscaecimuris, Lactobacillus taiwanensis, and Lactobacillus animals following RHSD administration. Furthermore, metabolomics profiling showed that the levels of gut microbiome metabolites were reversed after RHSD treatment, and differential metabolites were significantly correlated with motor function and intestinal function in PD mice. The integrated analysis of microbial metabolites and host transcriptomics suggested that abnormal amino acid metabolism, mitochondrial dysfunction, oxidative stress, and neuroinflammation in the PD model were associated with the diffusion of abnormal metabolites. This study illustrates the profound impact of RHSD administration on rectifying gut microbiota dysbiosis and improving the A53T mouse model. Notably, we observed significant alterations in the proliferation and metabolism of multiple probiotic strains of Lactobacillus. Furthermore, our research supports the hypothesis that microbiota-related metabolites may regulate the transcription of host genes, including dopamine receptors and calcium stabilization. Consequently, our findings underscore the potential of RHSD as a promising therapeutic candidate for the treatment of PD through the modulation of several signaling pathways within the microbiota-gut-brain axis.

ProRefiner: an entropy-based refining strategy for inverse protein folding with global graph attention.

Inverse Protein Folding (IPF) is an important task of protein design, which aims to design sequences compatible with a given backbone structure. Despite the prosperous development of algorithms for this task, existing methods tend to rely on noisy predicted residues located in the local neighborhood when generating sequences. To address this limitation, we propose an entropy-based residue selection method to remove noise in the input residue context. Additionally, we introduce ProRefiner, a memory-efficient global graph attention model to fully utilize the denoised context. Our proposed method achieves state-of-the-art performance on multiple sequence design benchmarks in different design settings. Furthermore, we demonstrate the applicability of ProRefiner in redesigning Transposon-associated transposase B, where six out of the 20 variants we propose exhibit improved gene editing activity.

Identification of the Microbial Transformation Products of Secoisolariciresinol Using an Untargeted Metabolomics Approach and Evaluation of the Osteogenic Activities of the Metabolites.

Secoisolariciresinol (SECO) is one of the major lignans occurring in various grains, seeds, fruits, and vegetables. The gut microbiota plays an important role in the biotransformation of dietary lignans into enterolignans, which might exhibit more potent bioactivities than the precursor lignans. This study aimed to identify, synthesize, and evaluate the microbial metabolites of SECO and to develop efficient lead compounds from the metabolites for the treatment of osteoporosis. SECO was fermented with human gut microbiota in anaerobic or micro-aerobic environments at different time points. Samples derived from microbial transformation were analyzed using an untargeted metabolomics approach for metabolite identification. Nine metabolites were identified and synthesized. Their effects on cell viability, osteoblastic differentiation, and gene expression were examined. The results showed that five of the microbial metabolites exerted potential osteogenic effects similar to those of SECO or better. The results suggested that the enterolignans might account for the osteoporotic effects of SECO in vivo. Thus, the presence of the gut microbiota could offer a good way to form diverse enterolignans with bone-protective effects. The current study improves our understanding of the microbial transformation products of SECO and provides new approaches for new candidate identification in the treatment of osteoporosis.

Comparison of the adjuvant effect of conbercept intravitreal injection at different times before vitrectomy for proliferative diabetic retinopathy.

Purpose: To assess the optimal time of intravitreal conbercept (IVC) treatment prior to pars plana vitrectomy (PPV) in patients with severe proliferative diabetic retinopathy (PDR). Method: This study was exploratory in nature. Forty-eight consecutive patients (48 eyes) with PDR were divided into four groups according to different IVC times (0.5 mg/0.05 mL) before PPV: group A (3 days), group B (7 days), group C (14 days), and group D (non-IVC). Intraoperative and postoperative effectiveness were assessed, and vitreous VEGF concentrations were detected. Result: For intraoperative effectiveness, groups A and D had a higher incidence of intraoperative bleeding than groups B and C (P = 0.041). Furthermore, groups A-C required less surgical time than group D (P < 0.05). For postoperative effectiveness, group B had a significantly higher proportion of visual acuity that improved or remained unchanged than group D (P = 0.014), and groups A-C had lower proportions of postoperative bleeding than group D. The vitreous VEGF concentration of group B (67.04 ± 47.24 pg/mL) was significantly lower than that of group D (178.29 ± 110.50 pg/mL) (P = 0.005). Conclusion: IVC treatment that was administered 7 days preoperatively was associated with better effectiveness and a lower vitreous VEGF concentration than its administration at other time points.

Spontaneous regression of secondary vitreoretinal lymphoma after diagnostic vitrectomy: case report.

PURPOSE: Our purpose is to report a patient with secondary intraocular mucosa-associated lymphoid tissue (MALT) who experienced spontaneous regression after diagnostic vitrectomy. METHODS: We retrospectively reviewed the clinical and imaging features of the case. Multimodal imaging, including fundus photograph, optical coherence tomography, fundus fluorescein angiography and ultrasound scan was presented. RESULTS: A 71-year-old female presented with a subretinal lesion temporal to macula and scattered multifocal creamy lesions deep to retina in her left eye. Optical coherence tomography of the left eye showed multifocal nodular hyper-reflective signals between the Bruch's membrane and RPE. She had a history of gastric MALT lymphoma. Diagnostic vitrectomy was performed. IL-10 level of aqueous was 187.7pg/ml. Cytology, gene rearrangement and flow cytometry of the vitreous were inconclusive. Systemic evaluation was normal. Secondary vitreoretinal MALT lymphoma was considered. Interestingly, her subretinal lesions regressed gradually without any chemotherapy. And IL-10 level of aqueous declined to 64.3pg/ml. CONCLUSIONS: Secondary vitreoretinal MALT lymphoma is extremely rare. Spontaneous regression of intraocular lymphoma does occur.

NEDD4L inhibits migration, invasion, cisplatin resistance and promotes apoptosis of bladder cancer cells by inactivating the p62/Keap1/Nrf2 pathway.

PURPOSE: This study identified the function of neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L) on bladder cancer (BLCA). METHODS: NEDD4L expression in BLCA patients was scrutinized. The function of NEDD4L on the viability, apoptosis, migration and invasion of BLCA cells was evaluated by cell counting kit-8, flow cytometry and Transwell assays. The effect of NEDD4L on the cisplatin (DDP) resistance of the DDP-resistant BLCA cells was explored. The influence of NEDD4L on the p62/Keap1/Nrf2 pathway activity in BLCA cells was tested by Western blot. Rescue experiments were implemented to verify whether NEDD4L regulated BLCA cell malignant behavior by mediating the Keap1/Nrf2 pathway activity via p62. The effect of NEDD4L on the growth and the p62/Keap1/Nrf2 pathway activity in vivo was researched in xenograft tumor nude mice models. RESULTS: The down-regulated NEDD4L in BLCA patients was associated with unfavorable survival. NEDD4L suppressed the viability (inhibition rate 57.1%/49.0%), migration (inhibition rate 49.7%/77.1%), invasion (inhibition rate 50.6%/75.7%), promoted the apoptosis of T24/5637 cells (promotion rate 243.8%/201.9%), reduced IC 50 of DDP-resistant T24/5637 cells from 132.2/101.8 to 57.81/59.71 µM, respectively, and inactivated the p62/Keap1/Nrf2 pathway in T24/5637 cells. p62 up-regulation partially abrogated the inhibition of NEDD4L on the Keap1/Nrf2 pathway activity, the malignant behavior of BLCA cells, and the DDP resistance of DDP-resistant BLCA cells. NEDD4L overexpression inhibited the tumor growth and the p62/Keap1/Nrf2 pathway activity in vivo in BLCA. CONCLUSION: NEDD4L inhibits the progression of BLCA by inactivating the p62/Keap1/Nrf2 pathway. It may be an effective target for BLCA treatment.

A Fast and Low-Power Detection System for the Missing Pin Chip Based on YOLOv4-Tiny Algorithm.

In the current chip quality detection industry, detecting missing pins in chips is a critical task, but current methods often rely on inefficient manual screening or machine vision algorithms deployed in power-hungry computers that can only identify one chip at a time. To address this issue, we propose a fast and low-power multi-object detection system based on the YOLOv4-tiny algorithm and a small-size AXU2CGB platform that utilizes a low-power FPGA for hardware acceleration. By adopting loop tiling to cache feature map blocks, designing an FPGA accelerator structure with two-layer ping-pong optimization as well as multiplex parallel convolution kernels, enhancing the dataset, and optimizing network parameters, we achieve a 0.468 s per-image detection speed, 3.52 W power consumption, 89.33% mean average precision (mAP), and 100% missing pin recognition rate regardless of the number of missing pins. Our system reduces detection time by 73.27% and power consumption by 23.08% compared to a CPU, while delivering a more balanced boost in performance compared to other solutions.

Three-dimensional evaluation of the mandibular condyle in adults with various skeletal patterns.

Objective: Morphometric and morphological evaluation of the mandibular condyle in adults and to identify its correlation with skeletal malocclusion patterns. Methods: Cone-beam computed tomography scans of 135 adult patients were used in this study and classified into groups according to four criteria: (1) sex (male and female); (2) sagittal skeletal discrepancy (Class I, Class II, and Class III); (3) vertical skeletal discrepancy (hyperdivergent, normodivergent, and hypodivergent); and age (group 1 ≤ 20 years, 21 ≤ group 2 < 30, and group 3 ≥ 30 years). The morphometrical variables were mandibular condyle height and width, and the morphological variable was the mandibular condyle shape in coronal and sagittal sections. Three-dimensional standard tessellation language files were created using itk-snap (open-source software), and measurements were performed using Meshmixer (open-source software). Results: The mandibular condyle height was significantly greater (p < 0.05) in patients with class III malocclusion than in those with class I or II malocclusion; the mandibular condyle width was not significantly different among different sexes, age groups, and sagittal and vertical malocclusions. There were no statistical associations between various mandibular condyle shapes and the sexes, age groups, and skeletal malocclusions. Conclusions: The condylar height was greatest in patients with class III malocclusion. The condylar height and width were greater among males than in females. The mandibular condyle shapes observed in sagittal and coronal sections did not affect the skeletal malocclusion patterns.

Identifying Prognostic Biomarkers Related to m6A Modification and Immune Infiltration in Renal Cell Carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is the largest category of kidney tumors and usually does not have a good prognosis. N6-methyladenosine(m6A) and immune infiltration have received increased attention because of their great influence on the clinical outcome and prognosis of cancer patients. METHODS: We identified hub genes through multi-dimensional screening, including DEGs, PPI analysis, LASSO regression, and random forest. Meanwhile, GO/KEGG enrichment, cMAP analysis, prognostic analysis, m6A prediction, and immune infiltration analysis were performed to understand the potential mechanism and screen therapeutic drugs. RESULTS: We screened 275 downregulated and 185 upregulated genes using three GEO datasets and the TCGA dataset. In total, 82 candidate hub genes were selected using STRING and Cytoscape. Enrichment analysis illustrated that the top 3 biological process terms and top 1 KEGG term were related to immunity. cMAP analysis showed some antagonistic molecules can be candidate drugs for the treatment of RCC. Then, six hub genes (ERBB2, CASR, P2RY8, CAT, PLAUR, and TIMP1) with strong predictive values for prognosis and clinicopathological features were selected. Meanwhile, P2RY8, ERBB2, CAT, and TIMP1 may obtain m6A modification by binding METTL3 or METTL14. On the other hand, differential expression of CAT, ERBB2, P2RY8, PLAUR, and TIMP1 affects the infiltration of the majority of immune cells. CONCLUSIONS: We identified six hub genes through multi-dimensional screening. They all possess strong predictive value for prognosis and clinicopathological features. Meanwhile, hub genes may regulate the progression of RCC via an m6A- and immunity-dependent mechanism.